What’s up? The most highly cited paper from 2005 is a review by Tanzi and Bertram, “Twenty years of the Alzheimer’s disease amyloid hypothesis: a genetic perspective”. It discusses the history of the evidence for the amyloid hypothesis, mostly in the context of genetic mutations that have been associated with the disease. Perhaps 2005 represented the peak of the (insoluble) beta amyloid hypothesis, and now the field is retooling?